Aging is associated with progressive lose of skeletal muscle mass and strength referred to as sarcopenia, a significant risk factor for disability, fraily, and mortality. Epidemiologically, muscle weakness defined based on a single measurement of hand grip strength has repeatedly proven to correlate with subsequent adverse health outcomes, even when measured in mid-life to predict physical disability decades later. These findings have led to ongoing efforts to define clinically meaningful cut points for muscle strength in the diagnosis of sarcopenia and growing interest in using grip strength as a key endpoint in clinical trials of new interventions for frailty. However, the success of such efforts requires improved knowledge in two areas. First, whether a single measurement of strength can sufficiently capture the underlying risk? Second, given that most of the pilot trials have a short follow-up, typically 6 months; it is important to know the degree and heterogeneity of detectable change in the short term and the clinical relevance of such change to long-term health outcomes. So far, these topics have not been adequately studied in a longitudinal setting. The central hypothesis is that short term trajectory of grip strength, characterized by rate of change and intra-person variability in grip strength, predicts long term trajectory of grip strength and adverse health outcomes in older adults. To test this hypothesis, this project proposes to evaluate: (i) the heterogeneity of short-term (6-month) trajectory of grip strength, (ii) the impac of short-term trajectory of grip strength on long-term (3- year) trajectories of health outcomes, and (iii) the effect of multisystem physiological dysregulation on short-term trajectory of grip strength. The study applies state-of-the-art statistical models to analyze existing longitudinal data from the Weekly Disability Substudy of the Women's Health and Aging Study (WHAS ) I. The substudy is comprised of 102 women aged 65 years and over who were evaluated on a weekly basis over six months, followed by additional five semi-annual visits of 6 months apart for a total follow-up of three years between 1993 and 1996. PUBLIC HEALTH RELEVANCE: This study is designed to break new grounds in understanding the clinical relevance of temporal changes in hand grip strength and their likely causes and consequences in older women. The results will provide useful risk assessment information to patients, families and clinicians, and preliminary data to define target population and treatment goals for future intervention studies on muscle strength in older adults.